AB0463 THE IMPACT OF PHARMACOVIGILANCE RISK ASSESSMENT COMMITTEE (PRAC) RECOMMENDATIONS ON THE REAL-LIFE USE OF JANUS KINASES INHIBITORS FOR RHEUMATOID ARTHRITIS
Authors: E. G. Favalli, M. Ferrito, R. DI Taranto, M. Biggioggero, F. Orsini, S. Germinario, G. Cincinelli, R. Caporali
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> In November 2022 the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) recommended measures to minimize the risk of serious adverse events associated with the use of Janus kinase inhibitors (JAKis). <h3>Objectives</h3> The aim of the study was to evaluate in a real-life cohort the impact of PRAC recommendations on the use of JAKis for the treatment of patients with rheumatoid arthritis (RA) and to describe their clinical characteristics. The rate of JAKi discontinuation because of major cardiovascular (CV) events (MACE), venous thromboembolism (VTE), or cancer was also analyzed according to PRAC limitations. <h3>Methods</h3> We conducted a retrospective analysis of RA patients treated with a JAKi from a single-centre, tertiary care hospital. The study population was stratified into patients eligible or not to JAKis in accordance with PRAC indications. We considered as ineligible: patients &gt;65 years old; current or former long-term smokers; patients carrying increased risk of MACE (defined according to ORAL SURVEILLANCE trial<sup>[1]</sup> inclusion criteria [&gt;50 years old and having at least one CV risk factor]), VTE (according to International Society on Thrombosis and Haemostasis categorization<sup>[2]</sup>), or cancer (defined as previous history of malignancy). In the ineligible group, a descriptive analysis of individual reasons for contraindication to JAKis was conducted. An analysis of reasons for JAKi discontinuation was performed in the whole population over a mean follow-up period of 20.9 months. <h3>Results</h3> Of 194 patients enrolled, 114 (57.9%) were classified as ineligible according to the PRAC definition (n=39 [34.2%] &gt;65 years old; n=80 [70.2%] at increased risk of MACE; n=35 [30.7%] smokers; n=23 [20.2%] at increased risk of VTE, n=8 [7.0%] with history of malignancy). As detailed in Table 1, 52 (45.6%) patients fulfilled only one, 49 (43.0%) two, and 13 (11.4%) three or more PRAC criteria. Among patients ineligible for a single factor, this was high risk of MACE in 42.3% of cases. Compared with eligible ones, ineligible patients were more often obese (18.4% vs 0%; <i>p</i>&lt;0,001), had a higher mean disease duration (15 vs 12 years; <i>p</i>=0.01), JAKis therapy duration (17.5 vs 10 months; p=0.02), mean HAQ score (1 vs 0.125; <i>p</i>&lt;0.001), and prevalence of arterial hypertension (43% vs 12.5%; <i>p</i>&lt;0.001), non-ischaemic heart disease (13.2% vs 3.8%; <i>p</i>=0.03), hyperlipidemia (53.5% vs 12.5%; <i>p</i>&lt;0.001), and diabetes (7.9% vs 1,3%; p=0.04). The discontinuation rate due to adverse events was similar in eligible (5.0%) and non-eligible (7.0%) patients (p=0.57). We observed two withdrawals for VTE, one withdrawal for non-fatal stroke and one for solid malignancy (all in the ineligible group). <h3>Conclusion</h3> Our analysis shows that rigorous application of PRAC recommendations in a real-life setting would result in a large proportion of RA patients being excluded from treatment with JAKis, apparently without a consequent significant reduction in the rate of serious adverse events. A better quantification of the risk for MACE, VTE, and malignancy is advocated to improve our decision-making process in the management of RA. <h3>References</h3> [1] Ytterberg SR, et al. N Engl J Med 2022 27;386(4):316-326. [2] Kearon C, et al. J Thromb Haemost 2016;14:1480–83. <h3>Acknowledgements</h3> We thank the physicians and patients who participated in this study. <h3>Disclosure of Interests</h3> Ennio Giulio Favalli Speakers bureau: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Matteo Ferrito: None declared, Raffaele Di Taranto: None declared, Martina Biggioggero Speakers bureau: Galapagos, Francesco Orsini: None declared, Sabino Germinario: None declared, Gilberto Cincinelli: None declared, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, UCB.